Evidence map›Paper›PMID 34625552›Full record

ArticleNature communications2021

Human cell based directed evolution of adenine base editors with improved efficiency.

Junhao Fu, Qing Li, Xiaoyu Liu, Tianxiang Tu, Xiujuan Lv, Xidi Yin, Jineng Lv, Zongming Song, Jia Qu, Jinwei Zhang and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.2field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Correcting a patient-specific Rhodopsin mutation with adenine base editor in a mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  6. Review
  7. Targeted mutagenesis of specific genomic DNA sequences in animals for thebioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Deconstructing cancer with precision genome editing.Biochemical Society transactions · 2024
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. A precise and efficient adenine base editor.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  20. Highly efficient A-to-G base editing by ABE8.17 in rabbits.Molecular therapy. Nucleic acids · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Junhao Fu *School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Qing Li *State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-6392-9699
Xiaoyu Liu *School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Tianxiang Tu *School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Xiujuan LvSchool of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Xidi YinState Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
Jineng LvSchool of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Zongming SongSchool of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.ORCID 0000-0001-5869-7312
Jia QuSchool of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Jinwei ZhangLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0002-2114-173X
Jinsong LiState Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China. jsli@sibcb.ac.cn.ORCID 0000-0003-3456-662X
Feng GuSchool of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China. gufenguw@gmail.com.ORCID 0000-0002-9600-8407
Wenzhou Medical University · CNChinese Academy of Sciences · CNHenan University · CNNational Institutes of Health · US

Funding

Noncoding RNA structures and interactions in cellular stress responses and immunityZIADK075136 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI ZHANG, JINWEI · 2016 to 2025
$23.2M
Intramural NIH HHS ZIA DK075136
6 · The paper itself

Abstract

Adenine base editors (ABE) are genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion. However, the low activity of ABE at certain sites remains a major bottleneck that precludes efficacious applications. Here, to address it, we develop a directional screening system in human cells to evolve the deaminase component of the ABE, and identify three high-activity NG-ABEmax variants: NG-ABEmax-SGK (R101S/D139G/E140K), NG-ABEmax-R (Q154R) and NG-ABEmax-K (N127K). With further engineering, we create a consolidated variant [NG-ABEmax-KR (N127K/Q154R)] which exhibit superior editing activity both in human cells and in mouse disease models, compared to the original NG-ABEmax. We also find that NG-ABEmax-KR efficiently introduce natural mutations in gamma globin gene promoters with more than four-fold increase in editing activity. This work provides a broadly applicable, rapidly deployable platform to directionally screen and evolve user-specified traits in base editors that extend beyond augmented editing activity.

Indexed as

AdenineGene EditingAnimalsDisease Models, AnimalFemalegamma-GlobinsGenetic TherapyHEK293 CellsHumansMaleMiceMice, Inbred C57BLPhenotypeAdeninegamma-Globins

Identifiers

PMID34625552
PMCPMC8501064
OpenAlexW3164694797

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.